Generation of two Betacellulin CRISPR-Cas9 knockout hiPSC lines to study the affected EGF system paradigm in schizophrenia

Several members of the epidermal growth factor (EGF) family have been implicated in the biology of schizophrenia (Ketharanathan et al., 2024). The EGF-related ligand, Betacellulin (BTC), plays an important role in the proliferation and differentiation of neural stem cells and our group found markedl...

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Main Authors: Agustin Cota-Coronado, Murray Manning, Dong-Hyung Kim, Joohyung Lee, Andrew Gibbons, Joseph Rosenbluh, Rachel A. Hill, Suresh Sundram
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Stem Cell Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506125001588
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author Agustin Cota-Coronado
Murray Manning
Dong-Hyung Kim
Joohyung Lee
Andrew Gibbons
Joseph Rosenbluh
Rachel A. Hill
Suresh Sundram
author_facet Agustin Cota-Coronado
Murray Manning
Dong-Hyung Kim
Joohyung Lee
Andrew Gibbons
Joseph Rosenbluh
Rachel A. Hill
Suresh Sundram
author_sort Agustin Cota-Coronado
collection DOAJ
description Several members of the epidermal growth factor (EGF) family have been implicated in the biology of schizophrenia (Ketharanathan et al., 2024). The EGF-related ligand, Betacellulin (BTC), plays an important role in the proliferation and differentiation of neural stem cells and our group found markedly reduced BTC levels in patients with schizophrenia. Nevertheless, the interplay of affected BTC and its participation in neural specification and neurodevelopment remains elusive. We generated Knockout (KO) − BTC clones from an existing hiPSC line through CRISPR/Cas9-mediated modification. Furthermore, we validated BTC-KO through genotyping/sequencing, FACS and Western Blot. Finally, we demonstrated trilineage differentiation potential in vitro.
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institution Kabale University
issn 1873-5061
language English
publishDate 2025-10-01
publisher Elsevier
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series Stem Cell Research
spelling doaj-art-89a8090c30a04f22a45464f76d17151c2025-08-24T05:12:00ZengElsevierStem Cell Research1873-50612025-10-018810380810.1016/j.scr.2025.103808Generation of two Betacellulin CRISPR-Cas9 knockout hiPSC lines to study the affected EGF system paradigm in schizophreniaAgustin Cota-Coronado0Murray Manning1Dong-Hyung Kim2Joohyung Lee3Andrew Gibbons4Joseph Rosenbluh5Rachel A. Hill6Suresh Sundram7Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia; Corresponding author.Cancer Research Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia; Functional Genomics Platform, Monash University, Clayton, VIC, AustraliaDepartment of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, AustraliaDepartment of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia; Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3168, AustraliaDepartment of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, AustraliaCancer Research Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia; Functional Genomics Platform, Monash University, Clayton, VIC, AustraliaDepartment of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, AustraliaDepartment of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia; Mental Health Program, Monash Health, Clayton, Victoria 3168, AustraliaSeveral members of the epidermal growth factor (EGF) family have been implicated in the biology of schizophrenia (Ketharanathan et al., 2024). The EGF-related ligand, Betacellulin (BTC), plays an important role in the proliferation and differentiation of neural stem cells and our group found markedly reduced BTC levels in patients with schizophrenia. Nevertheless, the interplay of affected BTC and its participation in neural specification and neurodevelopment remains elusive. We generated Knockout (KO) − BTC clones from an existing hiPSC line through CRISPR/Cas9-mediated modification. Furthermore, we validated BTC-KO through genotyping/sequencing, FACS and Western Blot. Finally, we demonstrated trilineage differentiation potential in vitro.http://www.sciencedirect.com/science/article/pii/S1873506125001588
spellingShingle Agustin Cota-Coronado
Murray Manning
Dong-Hyung Kim
Joohyung Lee
Andrew Gibbons
Joseph Rosenbluh
Rachel A. Hill
Suresh Sundram
Generation of two Betacellulin CRISPR-Cas9 knockout hiPSC lines to study the affected EGF system paradigm in schizophrenia
Stem Cell Research
title Generation of two Betacellulin CRISPR-Cas9 knockout hiPSC lines to study the affected EGF system paradigm in schizophrenia
title_full Generation of two Betacellulin CRISPR-Cas9 knockout hiPSC lines to study the affected EGF system paradigm in schizophrenia
title_fullStr Generation of two Betacellulin CRISPR-Cas9 knockout hiPSC lines to study the affected EGF system paradigm in schizophrenia
title_full_unstemmed Generation of two Betacellulin CRISPR-Cas9 knockout hiPSC lines to study the affected EGF system paradigm in schizophrenia
title_short Generation of two Betacellulin CRISPR-Cas9 knockout hiPSC lines to study the affected EGF system paradigm in schizophrenia
title_sort generation of two betacellulin crispr cas9 knockout hipsc lines to study the affected egf system paradigm in schizophrenia
url http://www.sciencedirect.com/science/article/pii/S1873506125001588
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